Prostaglandin E2 Reverses Aberrant Production of an Inflammatory Chemokine by Microglia from Sandhoff Disease Model Mice through the cAMP-PKA Pathway

Background: Sandhoff disease (SD) is a neurodegenerative lysosomal b-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including terminal GlcNAc-oligosaccharides and GM2 ganglioside. Microglia-mediated neuroinflammation contributes to the pathogenesis and progression of SD. Our previous study demonstrated that MIP-1a, a putative pathogenic factor for SD, is up-regulated in microglial cells derived from SD model mice (SD-Mg) through activation of Akt and JNK. Methodology/Principal Findings: In this study, we first demonstrated that prostaglandin E2 (PGE2), which is one of the lipid mediators derived from arachidonic acid and is known to suppress activation of microglia, reduced the aberrant MIP-1a production by SD-Mg to the same level as by WT-Mg. PGE2 also attenuated the activation of Akt and JNK. The inhibition of MIP-1a production and the activation of Akt and JNK occurred through the EP2 and 4/cAMP/PKA signaling pathway in the murine microglia derived from SD model mice. Conclusions/Significance: We propose that PGE2 plays a role as a negative regulator of MIP-1a production in th

人総研シンポジウム抄録 : 福島原発事故12年の経験から学ぶ -当時小学生だった若者達との対話から(第2回)-

departmental bulletin pape

Natural killer cells: walking three paths down memory lane

Immunological memory has traditionally been regarded as a unique feature of the adaptive immune response, mediated in an antigen-specific manner by T and B lymphocytes. All other hematopoietic cells, including natural killer (NK) cells, are classified as innate immune cells, which have been considered short-lived but can respond rapidly against pathogens in a manner not thought to be driven by antigen. Interestingly, NK cells have recently been shown to survive long term after antigen exposure and subsequently mediate antigen-specific recall responses. In this review, we address the similarities between, and the controversies surrounding, three major viewpoints of NK memory that have arisen from these recent studies: (i) mouse cytomegalovirus (MCMV)-induced memory; (ii) cytokine-induced memory; and (iii) liver-restricted memory cells

The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression

Fibrotic diseases, such as systemic sclerosis (SSc), idiopathic pulmonary fibrosis, renal fibrosis and liver cirrhosis are characterized by tissue overgrowth due to excessive extracellular matrix (ECM) deposition. Fibrosis progression is caused by ECM overproduction and the inhibition of ECM degradation due to several events, including inflammation, vascular endothelial dysfunction, and immune abnormalities. Recently, it has been reported that urokinase plasminogen activator (uPA) and its receptor (uPAR), known to be fibrinolytic factors, orchestrate the inflammatory response, vascular homeostasis, and immune homeostasis system. The uPA/uPAR system may show promise as a potential therapeutic target for fibrotic diseases. This review considers the role of the uPA/uPAR system in the progression of fibrotic diseases

α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis

Systemic sclerosis is a connective tissue disease of unknown origin that is characterized by immune system abnormalities, vascular damage, and extensive fibrosis of the skin and visceral organs. α2-antiplasmin is known to be the main plasmin inhibitor and has various functions such as cell differentiation and cytokine production, as well as the regulation of the maintenance of the immune system, endothelial homeostasis, and extracellular matrix metabolism. The expression of α2-antiplasmin is elevated in dermal fibroblasts from systemic sclerosis patients, and the blockade of α2-antiplasmin suppresses fibrosis progression and vascular dysfunction in systemic sclerosis model mice. α2-antiplasmin may have promise as a potential therapeutic target for systemic sclerosis. This review considers the role of α2-antiplasmin in the progression of systemic sclerosis

Preparation of Au nanowire films by electrodeposition using mesoporous silica films as a template: vital effect of vertically oriented mesopores on a substrate

Films consisting of polycrystalline Au nanowires were prepared by electrodeposition using mesoporous silica films with vertically oriented mesochannels as a template. The importance of the mesostructure near the surface of the substrate is emphasized by the comparison of films possessing vertically aligned mesochannels to the substrate with those having parallel aligned mesochannels from the viewpoints of Au deposition in the films and the presence or absence of the resulting cracking. When all mesopores lie parallel to the substrate, the mesoporous film was cleaved by the deposition of Au, which is in clear contrast to the case of Pt deposition. Fabricated Au nanowires are not interconnected with each other unlike Pt, irrespective of the presence of interconnected micropores

Pyocyanin stimulates membrane vesicle formation in Pseudomonas aeruginosa, but the synthesis is not required for enhanced vesiculation in biofilms

Bacterial membrane vesicles (MVs), particularly outer membrane vesicles (OMVs) in gram-negative bacteria, package their cargo for delivery to other bacteria or host cells. MV production is activated in the multicellular biofilm growth mode; however, the underlying mechanisms of enhanced MV production in biofilms are not fully understood. Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic infections due to biofilm formation, making it difficult to treat. Pyocyanin is a phenazine synthesized by P. aeruginosa, which is a blue-pigment signaling molecule and generates H2O2. Herein, we investigated the interplay among pyocyanin, H2O2, and MVs in P. aeruginosa biofilms. Pyocyanin, H2O2, and MVs were sequentially produced in P. aeruginosa static liquid biofilms, and all phenotypes were repressed in a biofilm-deficient mutant ∆pelA∆pslA, which does not synthesize extracellular polysaccharides Pel and Psl. The addition of pyocyanin increased H2O2 generation and MV formation, suggesting that pyocyanin-mediated H2O2 generation facilitated MV formation in P. aeruginosa. Because catalase repressed MV formation in the biofilm, it suggested that oxidative stress may be a pathway for the activation of MV production in P. aeruginosa biofilms. On the other hand, MV formation in biofilms was not increased in the mutant of phzM, which encodes an enzyme for pyocyanin synthesis. Thus, while additional pyocyanin promotes MV formation, several factors other than pyocyanin, such as extracellular polysaccharides, play a major role in enhanced MV formation in P. aeruginosa biofilms. Our study provides new insights into vesiculation in P. aeruginosa biofilms